Arch Neurol. 2011 May;68(5):599-606 doi: 10.1001/archneurol.2011.94.

Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials

Atri A, O'Brien JL, Sreenivasan A, Rastegar S, Salisbury S, DeLuca AN, O'Keefe KM, LaViolette PS, Rentz DM, Locascio JJ, Sperling RA.

Abstract

OBJECTIVE: To examine the feasibility and test-retest reliability of encoding-task functional magnetic resonance imaging (fMRI) in mild Alzheimer disease (AD).
DESIGN: Randomized, double-blind, placebo-controlled study.
SETTING: Memory clinical trials unit.
PARTICIPANTS: We studied 12 patients with mild AD (mean [SEM] Mini-Mental State Examination score, 24.0 [0.7]; mean Clinical Dementia Rating score, 1.0) who had been taking donepezil hydrochloride for more than 6 months from the placebo arm of a larger 24-week study (n = 24, 4 scans on weeks 0, 6, 12, and 24, respectively).
INTERVENTIONS: Placebo and 3 face-name, paired-associate encoding, block-design blood oxygenation level-dependent fMRI scans in 12 weeks.
MAIN OUTCOME MEASURES: We performed whole-brain t maps (P  RESULTS: Task tolerability and data yield were high (95 of 96 scans yielded favorable-quality data). Whole-brain maps were stable. Right and left hippocampal regions-of-interest intraclass correlation coefficients were 0.59 to 0.87 and 0.67 to 0.74, respectively. To detect 25.0% to 50.0% changes in week-0 to week-12 hippocampal activity using left-right extent or right magnitude with 80.0% power (2-sided α = .05) requires 14 to 51 patients. Using left magnitude requires 125 patients because of relatively small signal to variance ratios.
CONCLUSIONS: Encoding-task fMRI was successfully implemented in a single-site, 24-week, AD randomized controlled trial. Week 0 to 12 whole-brain t maps were stable, and test-retest reliability of hippocampal fMRI measures ranged from moderate to substantial. Right hippocampal magnitude may be the most promising of these candidate measures in a leveraged context. These initial estimates of test-retest reliability and power justify evaluation of encoding-task fMRI as a potential biomarker for signal of effect in exploratory and proof-of-concept trials in mild AD. Validation of these results with larger sample sizes and assessment in multisite studies is warranted.

PMID: 21555634